PROJECT 4/GAMBHIR PI: Gambhlr, Sanjiv S N3.4.1. Project Summary. Our long-term goals are to clinically translate nanodiagnostics {in vitro and in vivo) for the improved management of cancer patients. Our primary focus for this competing GONE renewal is on developing and using nanotechnology for earlier cancer detection/intervention, and for monitoring response to anti-neoplastic therapy. In the current proposal we focus on both ovarian and non-small cell lung cancers but expect that our strategies will eventually apply to many other cancers. We have made significant progress over the last cycle of this CCNE competing renewal grant including the development of Raman and photoacoustic molecular imaging strategies. In the last year we have also pursued translation of gold based Raman nanoparticles with endoscopic imaging for earlier colorectal cancer detection in patients. Both in vitro nanosensors and in vivo nano-molecular imaging will be utilized to accomplish our long-term goals. The combination of both in vitro and in vivo diagnostic strategies is expected to lead to a much greater accuracy and cost-effectiveness than either strategy alone. To translate our in vitro and in vivo diagnostic strategies we will utilize mouse models of human cancer that help us to test our approaches prior to clinical translation. The clinical translation will be accomplished through the help ofthe clinical translation core (Core 3) which links to various clinical trials and leverages on other funding mechanisms already in place in our CCNE. Two aims focused on ovarian and non-small cell lung cancer diagnostics will be pursued to accomplish our goals and are detailed next (Fig. N3.4.1).